Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 19 recordsLinked to original sources

PubMed1996

Intraoperative force-setting did not improve the mechanical properties of an augmented bone-tendon-bone anterior cruciate ligament graft in a goat model.

It has been hypothesized that load affects the mechanical properties of an anterior cruciate ligament graft while it remodels. The goal of this study was to use an existing goat model to evaluate the effect of intraoperative set force on the postoperative mechanical properties of an autograft that had been augmented with a synthetic segment. The following questions were addressed. Do augmented autografts set with a high force intraoperatively have improved structural and material graft properties and lower anterior-posterior knee laxity at 3 months after surgery, compared with autografts set with a low intraoperative force? How do the structural and material properties of these implanted autografts compare with the mechanical properties of an intact anterior cruciate ligament or an unimplanted control autograft? The anterior cruciate ligament was reconstructed in seven goats with use of a composite graft consisting of a bone-patellar tendon-bone autograft and a synthetic augmentation device. A force-setting technique was used intraoperatively to establish the load-sharing between the autograft and augmentation segments such that the autograft carried either a high (16.5 N in four animals) or low (1.5 N in three animals) level of force, while the total force in the composite graft remained constant. Tensile testing was performed at 3 months after surgery to determine the material and structural properties of the autograft, the intact anterior cruciate ligament from the normal contralateral knee, and a control bone-patellar tendon-bone graft of similar size that was harvested from the contralateral knee at the time of necropsy and had never been implanted in the joint. The structural and material properties of the autografts initially set to high or low loads at surgery were not significantly different after 3 months of implantation. The strength and stiffness of the implanted tendons were an average of 24 and 20% of the strength and stiffness of the normal anterior cruciate ligament and 31 and 62% of the control tendons, respectively. Intraoperative set force in an augmented anterior cruciate ligament graft at the levels chosen in this study did not significantly affect weakening of the autograft at 3 months.

Animals↗

PubMed1996

Treatment of resistant gestational choriocarcinoma with taxol: a report of two cases.

Two patients with resistant gestational choriocarcinoma were treated w with Taxol after extensive prior chemotherapy including EMACO and platinum-based salvage chemotherapy. Both patients showed significant responses to Taxol. One patient relapsed in the brain and liver after treatment and died. Taxol was combined with carboplatin in the other patient who achieved sustained clinical and hormonal remission after craniotomy and excision of resistant disease in the brain.

Adult↗

PubMed1996

Expression of A, B, and H blood group antigens in epithelial ovarian cancer: relationship to tumor grade and patient survival.

The expression of A, B, and H blood group antigens in epithelial ovarian cancer was evaluated in 137 patients with advanced disease by staining frozen sections with specific monoclonal antibodies using an indirect immunoperoxidase method. Expression of blood group antigens was observed in a proportion of ovarian carcinomas and in some areas of ovarian surface epithelium. Forty-eight percent of the tumors tested from 130 blood group A, B, or 0 individuals showed no expression of the appropriate blood group antigen, 32% had heterogeneous antigen expression, and 20% had strong expression. In the 7 blood group AB patients studied, no expression, heterogeneous expression of both antigens, or absence of one, but not the other antigen, was observed. No tumor showed A, B, or H antigen expression that was not compatible with the patient's blood group type. Histologic Grade 3 tumors showed absence of blood group antigen expression more often than did Grade 2 tumors. The presence or absence of A, B, or H antigen expression did not correlate with survival in this group of patients. This is in contrast to studies in other epithelial tumor types in which the normal epithelium synthesizes blood group antigens and loss of ABH antigen expression is observed in the corresponding tumors.

Aged↗

PubMed1996

A molecular anatomical analysis of mosaic trisomy 16.

A one-month-old child presenting with an aortic coarctation was found to have a left single transverse palmar crease and proportionate growth delay on physical examination, prompting a peripheral blood chromosome analysis. This showed a mosaic trisomy of chromosome 16, subsequently observed to decrease with the passage of time. As her phenotype was relatively benign, further analysis was performed to define more precisely the extent of her mosaicism given the supposedly lethal nature of the aneuploid cell line. Fluorescence in situ hybridisation and CA repeat polymorphism studies demonstrated the aneuploidy in multiple tissues, including the structurally affected aorta. Molecular analysis showed both maternal chromosomes 16 to be present in the trisomic cells, but maternal heterodisomy was not present in the diploid cells. Given the increasing number of individuals described with aneuploid mosaicism, we suggest that the study of multiple tissues is a necessary approach, the eventual goal being the appreciation of the relationship between the characteristics of a somatic mosaicism and the phenotype it imparts.

Alleles↗

PubMed1996

Abnormal kinetics of colony formation by erythroid burst-forming units (BFU-E) in chronic myeloid leukaemia.

We have investigated the kinetics of colony formation by progenitor cells in chronic myeloid leukaemia (CML) using erythroid burst-forming units (BFU-E) as a model system. For this, we scored the numbers of subcolonies produced by individual BFU-E in cultures of normal marrow and blood cells and in cultures of CML blood cells. The formation of an erythroid burst consisting of a single subcolony was taken as evidence for immediate terminal differentiation; the formation of multiple subcolonies was taken as evidence for commitment to terminal differentiation only after several cell generations. Therefore the probability of differentiation can be obtained by scoring the numbers of subcolonies in individual erythroid bursts. We found that the probability of differentiation is decreased (P = 0.0004) and the number of subcolonies increased (P = 0.01) in CML BFU-E compared with normal BFU-E. The cellularity of the BFU-E was also increased in CML. Using the probabilities of differentiation and renewal obtained from the BFU-E cultures the results fitted the predictions of a stochastic branching model. These results indicate that (a) commitment to terminal erythroid differentiation occurs over several cell generations in populations of BFU-E, (b) the probability of commitment to terminal differentiation (PD) within a particular population of BFU-E, remains a constant independent of the number of cell generations involved, (c) PD is lower during burst formation by CML BFU-E than by normal BFU-E, and (d) commitment to terminal differentiation occurs over more cell generations in CML burst formation than in normal burst formation. Therefore a reduced probability of differentiation may be a primary defect and could explain the expansion of the erythroid progenitor cell compartment in CML.

Bone Marrow↗

PubMed1996

Effect of chronic exposure to ultraviolet radiation and photoreactivation on life span and tumor development in the marsupial Monodelphis domestica.

The effect of exposure to chronic ultraviolet (UV) radiation on life span was examined in Monodelphis domestica, which is capable of photoreactivation repair of UV-radiation-induced pyrimidine dimers. Shaved Monodelphis were exposed to 500 J/m2 UV radiation, 500 J/m2 UV radiation then 90 min of photoreactivating light (PRL), or 90 min of PRL three times weekly for 104 weeks. Opossums were weighed weekly; samples for serum chemistry and hematology testing were obtained periodically. Complete postmortem examinations revealed a primary cause of death for each opossum. Meaningful differences among the groups in weight gain, serum chemistry values or hematology values were not seen. Significant life-shortening due to UV-radiation exposure was found for females but not males. Photoreactivation prolonged life only in the females exposed to UV radiation. Exposure to UV radiation was not associated with accelerated development of degenerative disease. Significant treatment-related mortality occurred in both male and female opossums exposed to UV radiation. Photoreactivation reduced the relative risk of skin tumors but not eye tumors in Monodelphis exposed to UV radiation. Eye and skin tumors were less likely to be a cause of death in UV-radiation-exposed opossums subsequently exposed to PRL than in opossums exposed to UV radiation alone. Females exposed only to UV radiation had an increased risk of skin tumor development relative to males.

Animals↗

PubMed1996

Phenotype and progeny of primitive adherent human hematopoietic progenitors.

Hematopoietic progenitor cells can be classified as plastic- and stroma-adherent (P+S+), stroma-adherent (P-S+) and non-adherent (P-S-). Both P+S+ and P-S+ populations are detected in delta (delta) culture systems where they produce non-adherent (P-S-) granulocyte-macrophage colony-forming cells (CFU-GM) and erythroid burst-forming units (BFU-E). Here we demonstrate that the plastic-adherent progenitor cells (P delta cells) comprise 5-10 percent of the CD34+, population in adult human marrow. Moreover, they do not express CD3 or CD22 and 88 percent of them are CD38-, 88 percent are CD33- and 74 percent are HLA-DR-. Production of CFU-GM by purified plastic-adherent CD34+, adherent cells was 60 percent of the number produced by recombined CD34+, and CD34- fractions. We have shown also that the plastic-adherent P+S+ cells are the precursors of the stroma-adherent P-S+ cells (S delta cells), day 21 cobblestone-area forming cells (CAFC) and cells capable of sustained hematopoiesis in a modified long-term bone marrow culture system. These observations support the primitive nature of P delta cells and establish a phenotypic sequence of plastic and stroma adherence through stroma adherence to non-adherence in hematopoietic cell development. To further investigate the relationship between P delta cells, S delta cells and long-term culture-initiating cells (LTCIC), we cultured whole mononuclear cell tractions and plastic-adherent cell-depleted mononuclear cell fractions in long-term culture and in the S delta assay. The results indicated the P delta cells were inhibited in the presence of stromal cells.

ADP-ribosyl Cyclase↗

PubMed1995

Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response.

Recurrent ovarian cancer after negative findings at second-look laparotomy is common. A retrospective review of 57 patients who developed recurrent tumor after a negative second-look laparotomy was undertaken to evaluate treatment efficacy and prognostic factors. All patients received primary platinum-based chemotherapy. Recurrences occurred in the abdomen or pelvis (40 patients), lymph nodes (7), liver (4), lungs (3), and vagina (3). Recurrent disease was diagnosed at a mean interval of 20 months after second-look surgery. Of the 38 patients who underwent laparotomy for recurrence, 36 (95%) had > 0.5 cm disease. After cytoreductive surgery 14 patients (37%) were left with minimal (< 0.5 cm) residual disease. Intestinal resection or bypass was performed on 10/38 patients (26%) with one requiring a colostomy. There was no operative mortality and one complication (small bowel obstruction). Treatment after recurrence consisted of platinum-based chemotherapy (88%), with the remaining patients receiving irradiation or hormonal therapy. At a mean follow-up from recurrence for the entire group of 20 months, 18/38 (47%) explored patients are alive. All 19 patients who were not explored died with a median survival time from recurrence of 9 months. Patients who underwent a laparotomy and patients with < 0.5 cm residual disease had a significant survival advantage (P < 0.0001). Initial stage, grade, disease-free interval, and disease found at laparotomy did not influence survival. Recurrent ovarian carcinoma after platinum-based chemotherapy is associated with a grave prognosis when the patient is deemed inoperable or when distant metastasis are found. Patients with disease reduced to < 0.5 cm showed a significant survival advantage.

Abdominal Neoplasms↗

PubMed1995

Platinum-based chemotherapy for advanced-stage serous ovarian carcinoma of low malignant potential.

PURPOSE: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. PATIENTS AND METHODS: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. RESULTS: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor < 2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. CONCLUSIONS: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.

Adult↗

PubMed1995

Design and biomechanics of a plate for the distal radius.

A dorsal plate for the distal radius was designed to provide rigid fixation and thus allow early motion. It functions as a blade plate, lessening the role of metaphyseal screws, and providing internal neutralization rather than compression. The rigidity and strength of the plate were compared to the existing T-plate in an unstable, extra-articular fracture model in paired, fresh-cadaver, axially loaded radii. The dorsal plate construct was significantly stronger and more rigid than the T-plate construct. The failure mode was similar for both plate types; 8 of 10 constructs failed with plate bending and screw loosening, while the oldest specimen pair showed primary bone failure. Compared to the T-plate, the dorsal plate transmitted a greater single axial load from the articular surface to the shaft.

Aged↗

PubMed1995

Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood.

Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P delta cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of P delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P delta progenitors to produce CFU-GM. Here we report that the frequencies of P delta progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10(5) mononuclear cells respectively) and individual cord blood P delta progenitors produce fewer CFU-GM than adult P delta progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the P delta cell population. The data indicate that P delta cells in cord blood have a higher PPR (0.59) than those in adult marrow (0.36). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore P delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P delta cells in adult marrow.

Adult↗

PubMed1995

Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids.

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML.

Apoptosis↗

PubMed1995

Induction of nasal carboxylesterase in F344 rats following inhalation exposure to pyridine.

Carboxylesterases (CEs) in the nasal mucosa metabolize some inhaled esters, including industrially important acrylates and acetates, to toxic acid metabolites that produce site-specific lesions in the nasal epithelium. The metabolic capacity of CEs in the normal nasal mucosa is theoretically sufficient to protect the lower respiratory tract from toxicant-induced injury at concentrations of acrylates and acetates likely to be inhaled in industrial environments. Thus, alterations in the metabolism and toxicity of these substrates would be predicted with changes in the amount or activity of CE in the nasal mucosa. Although many other nasal enzymes have been reported to be relatively refractory to induction, the amount of CE in the nasal mucosa can be increased by inhalant exposure. In the liver, expression of CEs may be elevated in response to exposure to P450 inducers. To examine this phenomenon in the nose with the widely used industrial solvent pyridine, we examined the effect of pyridine inhalation at the threshold limit value concentration of 5 ppm, or at 444 ppm, 6 hr/day for 4 days on the localization and amount of immunoreactive CE in olfactory mucosas of F344/N rats. CE immunoreactivity was increased in Bowman's glands following exposure to 5 or 444 ppm pyridine, and in sustentacular cells most notably following the 5 ppm exposure. Quantitative densitometry showed a statistically significant, dose-related increase in the density of immunoreactive CE in Bowman's glands of pyridine-exposed rats. These results indicate pyridine, and possibly other solvents, can induce nasal CE, an enzyme not directly involved in the metabolism of those solvents, following low-dose, short-term exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

Evidence for a mechanism that can provide both short-term and long-term haemopoietic repopulation by a seemingly uniform population of primitive human haemopoietic precursor cells.

One of the controversies surrounding the repopulating capacities of haemopoietic stem cells is whether or not the same or different populations are responsible for short-term and long-term repopulation after transplantation. To address this question, we analysed results obtained from an in vitro model for the clonal production of granulocyte-macrophage colony-forming cells (CFU-GM) by individual primitive multilineage precursors in adult human bone marrow. The primitive precursors adhere to plastic and produce CFU-GM in a 1-week long 'delta' type culture. The clones that form are classified as having short maturation pathways (clones containing predominantly day 7 CFU-GM) or long maturation pathways (clones containing predominantly day 21 CFU-GM). The results indicate that individual primitive (P delta) cells produce clones that reach full maturity after different periods of time so that cells corresponding to a range of maturational stages can become available simultaneously. Consequently, transplanted stem cells may be able to provide both rapid and long-term mature cell recovery whilst at the same time reconstituting the stem cell pool. These results suggest that it might be possible to use highly purified stem cell populations, devoid of committed progenitors, for clinical transplantation.

Bone Marrow Cells↗

PubMed1995

Dental practice considerations.

Treating young children, working through an intermediary (the parenting adult), obtaining informed consent, and reporting suspected child abuse bring extra pressures to the dentist and staff members unless the protocol for each step is established and followed precisely. Managing for fiscal soundness and making a profit are other professional responsibilities. Counterbalancing the many pressures, the dentist who treats young children enjoys an added measure of pleasure beyond that experienced by many colleagues by helping a young child cope with the stresses of treatment, leading a child into a lifetime free of dental disease, and winning the trust and approval of parents or guardians. All of these aspects make dentistry a profession that provides a lifetime of excitement, fulfillment, learning, and constant opportunities for growth.

Adult↗

PubMed1995

Expression of cell-surface lectins on haemopoietic progenitor cells.

The expression of lectins on the surface of the murine multi-myeloid progenitor cell line FDCP-Mix, and the human leukaemic cell line KG1, was assessed and compared to the pattern of lectin expression observed on human bone marrow mononuclear cells. Using flow cytometry, cell-surface lectins were identified by their ability to recognise fluorescein isothiocyanate-labelled neoglycoproteins. Both cell lines recognised neoglycoproteins expressing alpha-D-glucose and alpha-D-galactose residues. Inhibition studies suggested that recognition of these neoglycoproteins was via two independent receptors, each displaying characteristic sugar-binding properties. The CD34+ population of bone marrow mononuclear cells, identified by positive staining with the anti-CD34 antibody QBend10, were shown to interact with alpha-glucose-, alpha-galactose- and alpha-D-mannose-expressing neoglycoproteins. Similarly, binding of these probes to lymphocyte and monocyte sub-populations of CD34- bone marrow mononuclear cells was observed. In contrast, CD34- granulocytic cells did not appear to recognise these probes. It is suggested that the alpha-D-galactose binding activity observed for both cell lines and the alpha-D-galactose and alpha-D-mannose binding activity observed for bone marrow mononuclear cells represent expression of the component polypeptides of the previously reported galactosyl/mannosyl receptor. The glucosyl-specific receptor, observed on both cell lines and on bone marrow mononuclear cells, has not been reported previously. It is suggested that this receptor may mediate glucose transport or cell adhesion through recognition of glucosyl-containing compounds such as heparan sulphate.

Bone Marrow Cells↗

PubMed1994

An improved technique for measuring in vivo intervertebral motion in the canine.

STUDY DESIGN: An experimental animal study using an established technique for measuring in vivo motion in canines was designed to improve measurement techniques and to eliminate the effects of the instrument mounting technique on the tissue and subsequently on the motion being measured. OBJECTIVES: The purpose of this study was to improve a technique for measuring in vivo intervertebral motion in canines, so that the measuring technique did not affect the motion being measured. SUMMARY OF BACKGROUND DATA: Biplanar radiography has been used to measure in vivo intervertebral motion, but involves radiation exposure and expensive equipment. Electromechanical devices have been used more recently but have had significant effects on the motion over extended time periods. METHODS: Intervertebral motion was measured using an instrumented spatial linkage in eight adult canines divided into two groups that differed regarding the method of "mounting pin" placement. Group I had open surgical placement of the pins and Group II had pins placed into the spinous processes. After pin implantation, the instrumented spatial linkage was attached and motion data were recorded during walking. This testing sequence was repeated 3 weeks later. Animals were killed and intervertebral and facet motion were calculated from the experimental data and compared statistically. RESULTS: Facet motion decreased 1 to 3 weeks after pin implantation for animals of group I (3.4 +/- 0.2 mm to 1.1 +/- 0.3 mm), whereas the facet excursion of animals in Group II showed no change (3.0 +/- 0.2 mm and 3.1 +/- 0.3 mm). CONCLUSIONS: A new method of measuring in vivo intervertebral motion in canines has been developed and shown to have no significant affect on the segment mechanics.

Animals↗

PubMed1994

Comparison of in vivo and in vitro adjacent segment motion after lumbar fusion.

STUDY DESIGN: For in vitro studies, there is no basis for choosing a "load control study" over a "displacement control" study. This study qualitatively compared results from in vitro and in vivo tests, allowing the authors to address the experimental assumptions that in vitro testing contributes to the understanding of the in vivo condition. OBJECTIVES: To compare motion changes at segments adjacent to fusions for in vitro and in vivo tests. SUMMARY OF BACKGROUND DATA: Investigators have measured the effects of spinal fusions on the adjacent segment in a human cadaver model and found greater adjacent facet joint load after fusions. Others have found significant increases in motion and facet loads at segments adjacent to in vitro lumbosacral and long fusions, when the same range of motion was repeated before and after immobilization of lumbar segments. METHODS: L2-L3 motion was measured in vitro by an instrumented spatial linkage under load and displacement control before and after immobilization of segments (L3-L7). In vivo, L2-L3 motion was measured while animals walked on a treadmill. L3-L7 was fused and the L2-L3 motion testing was repeated. The change in in vivo adjacent segment motion was qualitatively compared with the in vitro change under "load" and "displacement" control. RESULTS: Under "load" control, in vitro facet motion did not significantly change after immobilization, whereas under "displacement" control, the facet motion significantly increased from 2.2 +/- 0.4 mm to 4.1 +/- 0.6 mm. Post-instrumentation, in vivo L2-L3 facet motion increased significantly. This change in vivo related better to the changes seen in the in vitro "displacement" control test than to the in vitro "load" control test.

Animals↗